The IBD interactome: an integrated view of aetiology, pathogenesis and therapy
The IBD interactome: an integrated view of aetiology, pathogenesis and therapy
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DOI：
10.1038/nrgastro.2017.110
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发表时间：
2017-12-01
影响因子：
65.1
通讯作者：
Iliopoulos, Dimitrios
中科院分区：
文献类型：
--
作者：
de Souza, Heitor S. P.;Fiocchi, Claudio;Iliopoulos, Dimitrios
克罗恩病和溃疡性结肠炎是由环境因素、基因组因素、微生物因素和免疫因素相互作用引起的以慢性、异质性表现为特征的典型复杂疾病。这些相互作用导致了压倒性的复杂性，不能通过孤立地研究每个病理组件的总体来解决，而不考虑所有相关的组之间的相互作用，从而产生总体的“网络效应”。这种效应的结果是‘IBD相互作用体’，定义为一个疾病网络，其中个体基因组的失调导致肠道炎症，由功能失调的分子模块介导。为了定义IBD互动组，需要新的概念和工具来实施系统方法；一种无偏见的数据驱动的集成战略，揭示系统的关键参与者，查明炎症的核心驱动因素，并使靶向治疗的开发成为可能。强大的生物信息学工具能够查询和整合多个基因组，使基因组、表观基因组、转录组、蛋白质组、代谢组和微生物组信息得以整合，以构建IBD的全面分子图谱。这一方法将有助于识别IBD分子亚型，与临床表型的相关性，并阐明IBD相互作用组的中心中心，这将有助于发现能够专门针对控制疾病的中心中心的化合物。
Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '-ome') in isolation without consideration of the interaction among all relevant - omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual - omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple - omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.